During industrial processing of Asparagus (Asparagus officinalis L.), around half of each spear is discarded. However, these discarded asparagus (by‐products) might be used as food supplements for their potential therapeutic effects. This study evaluated the hypolipidemic effect of n‐butanol extract (BEA) from asparagus by‐products in mice fed a high‐fat diet (HFD). Continuous HFD feeding caused hyperlipidemia, oxidative stress and liver damage in mice. Interestingly, while BEA significantly decreased the levels of body weight gain, serum total cholesterol and low density lipoprotein cholesterol, it dramatically increased the high density lipoprotein level when administered at three different doses (40, 80 or 160 mg/kg body weight) for 8 weeks in hyperlipidemic mice. In addition, BEA decreased the levels of alanine transaminase, aspartate transaminase and alkaline phosphatase in serum. Finally, superoxide dismutase activity and the total antioxidation capacity were evidently increased, while the malondialdehyde level and the distribution of lipid droplets were reduced in liver cells of BEA‐treated mice. Taken together, the findings of this study suggested that BEA had a strong hypolipidemic function and could be used as a supplement in healthcare foods and drugs or in combination with other hypolipidemic drugs.